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[A device for the drug-capsule administration into the rat stomach and its pharmacological application (author's transl)].

To assess the absorption of drugs given in capsule form to rats, the method of administration was studied using gastric-cannulated rats. The body weight of these rats remained the same as even when given casein hydrolysate and vitamins in addition to the usual chow diet. Indomethacin (IM) capsule (2 mg/capsule) was given and the plasma concentration and anti-inflammatory action of IM were studied. The maximum plasma concentration was seen at 2 hr after administration of one capsule. The carrageenin-induced edema of rat hind paw was inhibited with the ingestion of only one capsule. In addition, the time course of the plasma concentration of IM correlated with that of the inhibitory effect of carrageenin-induced edema. In the case of administration of a barium sulfate capsule to the cannulated rats, the transfer of the barium sulfate was clearly observed on the X-rays. Our findings suggest that this approach to the estimation of drugs is feasible, at least in experimental animals.

Animals↗

Permeability of lipid-coated polymer capsule membranes to solutes: effects of temperature and chemical structure of solutes.

The permeability of di-stearyldimethylammonium-coated polyamide capsule membranes to KCl, and tetra-methylammonium (4C1N), tetra-propylammonium (4C3N), and tetra-butylammonium (4C4N) bromides was investigated at temperatures below and above the phase transition temperature of the amphiphile coat and compared with that of non-coated polyamide capsule membranes. The rate of solute permeation through the non-coated capsule membranes for all permeants increased gradually with rise in temperature. When the capsule was coated with the amphiphile, the rate was reduced by a factor of 2-200 relative to that through the non-coated semipermeable capsule membranes and changed drastically or slightly at the phase transition temperature of the amphiphile coat, depending on the chemical structure of permeants. The permeation of hydrophilic KCl and slightly hydrophobic 4C1N was greatly supressed by the amphiphile coat below the phase transition temperature while it was enhanced above that temperature. On the contrary, the permeation rate of the moderately hydrophobic and bulky 4C3N increased monotonically with rising temperature. No change in the permeation rate was observed with the highly hydrophobic and bulky 4C4N at all temperatures.

Calorimetry, Differential Scanning↗

Rheology and filling characteristics of particulate dispersions in polymer melt formulations for liquid fill hard gelatin capsules.

The rheology and capsule filling properties of molten excipients, Dynafill, Dynasan-114. Lutrol-F68, and polyethylene glycols (PEG) 6000, 8000, 10,000, and 20,000 have been investigated. Lactose (alpha-monohydrate) was selected as a model particulate solid with low solubility in PEG in order to investigate the effects of disperse phase particle size, concentration, and PEG molecular weight on rheology and capsule filling properties of these systems. All excipients behaved as Newtonian fluids between 65 and 90 degrees C, which was chosen as a possible temperature range for liquid filling of hard gelatin capsules. The excipients, apart from Dynasan-114 and PEG 20,000, showed satisfactory capsule filling properties at 70 degrees C using a semi-automatic filling machine. Dynasan-114 (viscosity = 0.012 Pa.s at 70 degrees C) leaked from the seals between the hopper and pump of the filling machine, whereas PEG 20,000 (viscosity = 24 Pa.s at 70 degrees C) showed bridging of the molten polymer between successive capsule bodies during the filling process. The effect of disperse phase (lactose) particle size and concentration, and continuous phase (PEG) molecular weight on the apparent viscosity and filling properties of the non-Newtonian dispersions were investigated at 70 degrees C. Satisfactory filling of the dispersions was achieved at 70 degrees C up to a limiting concentration of disperse phase which was dependent upon disperse phase particle size and continuous phase molecular weight, and corresponded to a pronounced increase in apparent viscosity of the dispersion.

Capsules↗

In vitro performance of floating sustained-release capsule of verapamil.

Capsules filled with mixtures of verapamil, hydroxypropoxyl cellulose (HPC), and effervescent are proposed to provide floating sustained release over 10 hr. The effects of weight filled in the capsule, amount of HPC, and the addition of effervescent on the dissolution kinetics are studied. The conventional capsules were filled with different amounts and weights of the mixtures of verapamil, HPC, and effervescent. The release of verapamil from the capsules followed the Higuchi release model. However, when effervescent was added, a zero-order drug release was observed after the burst phase. The conventional capsule, when filled with active ingredients, polymers, and effervescent, can achieve a zero-order release system. Entrapped air was considered as a barrier to diffusion and matrix relaxation in drug release.

Air↗

Binding of FGF-1 and FGF-2 to heparan sulphate proteoglycans of the mammalian lens capsule.

In the mammalian eye, FGF plays a key role in the induction of lens fibre differentiation and, in other systems, heparan sulphate proteoglycans (HSPGs) have been shown to modulate FGF activity. HSPGs were isolated from the anterior and posterior rat and bovine lens capsule and assessed in terms of their ability to bind FGF-1 and FGF-2. In the rat, at least four HSPGs were identified with molecular weights of 142, 166, 200 and approximately 250 kD, the latter species predominating. The capsule HSPGs bound both FGF-1 and FGF-2. There appeared to be little, if any, competition for binding between FGF-1 and FGF-2. The capsule contained substantial amounts of core protein, which did not bind FGF, with a higher core protein/HSPG ratio in the anterior than in the posterior capsule. This was the only major HSPG-related difference noted between anterior and posterior capsule.

Animals↗

Theoretical modelling of the motion and deformation of capsules in shear flows.

Mechanical models for capsules freely suspended in another liquid, are devised to predict the deformation, motion, breakup of one particle and also the rheological flow behaviour of a suspension. The capsule is filled with a newtonian liquid, and is surrounded by a thin deformable membrane having otherwise arbitrary mechanical properties. Initially spherical capsules in simple shear flow, are found to deform and orient with respect to streamlines, while their membrane is continuously rotating around the internal liquid. A dilute suspension of such capsules has a viscoelastic constitutive law which depends on the particle physical properties. It is then possible to use such models to interpret experiments in terms of the mean intrinsic properties of a capsule population.

Capsules↗

Study of microencapsulation for pituitary transplantation: capsule preparation and in vitro study.

We have developed microcapsules using sodium alginate (SA) and Poly-L-Lysine (PLL). A factorial design method of screening was chosen to study influences of different experimental parameters on size and stability of the capsules. We found that air flow affects initial size of the capsules significantly, while the molecular weight (MW) of PLL and incubation time have a positive impact on the expansion when capsules are incubated in sodium citrate (SC). When the capsules were continuously shaken in an attempt to mimic in vivo environmental conditions, those capsules made with optimal parameters (0.1% PLL, 42,000 MW, incubated for 6 minutes; 1.5% SA, incubated for 4 minutes; SC bath 4 minutes; 25# needle; air flow 14L/min) were still intact after 30 days and not totally ruptured until 90 days, while those developed with less strict parameters were ruptured within 2 hours in 50%. We also encapsulated human pituitary adenoma cells using PLL of 80,000 MW and cultured them for 9 days. Adenoma cells, both encapsulated or non-encapsulated, secreted the same amount of hormones. Our preliminary study suggests that selecting optimal combinations of experimental parameters is essential in developing durable microcapsules, which may be potentially used for pituitary transplantation in vivo.

Adenoma↗

Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy.

AIM: To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS: Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS: Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control (16 min vs 70 min, P = 0.005), whereas the small bowel transit time was comparable between the two groups (227 min vs 183 min, P = 0.18). Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION: Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

Body Mass Index↗

Usefulness of capsule endoscopy in patients with suspected small bowel disease.

AIM: To study the usefulness and safety of capsule endoscopy as a diagnostic tool in various small bowel disorders. DESIGN: A retrospective analysis of a series of cases. MATERIAL AND METHODS: Between August 2001 and August 2002, 92 capsule endoscopy procedures were performed in 88 patients (53M/39F, age: 43.87 +/- 16.78). Indications included: chronic diarrhea (n=33); unknown abdominal pain (n=29); occult gastrointestinal bleeding or iron-deficiency anemia (n=13); abdominal discomfort in NSAID takers (n=7); staging of gastrointestinal tumors (n=4), and asymptomatic controls (n=2). Previously performed gastroscopy, colonoscopy, and small-bowel follow-through were not conclusive in all patients. RESULTS: Most frequently relevant findings included: jejuno-ileal aphtas and ulcerations (29 patients), vascular malformations (13 patients), and intestinal neoplasm (6 patients). The groups with a higher rate of findings related to this indication were occult gastrointestinal bleeding (76.92%) and chronic diarrhea (67.85%), with the lowest rate in the abdominal pain group (34.48%). Therapeutic strategy was directly changed in 36 of 88 patients (40.90%) because of capsule-endoscopic findings. The only observed complication was the failed excretion of one of the capsules because of an unknown ulcerated intestinal stricture. CONCLUSIONS: Capsule endoscopy is a safe procedure which can study the entire small bowel, meaning a valuable tool for the management of patients with suggestive signs and symptoms of intestinal disorders.

Adolescent↗

Previously unknown stricture due to radiation therapy diagnosed by capsule endoscopy.

Radiation enteritis is a complex clinical entity secondary to the affectation of intestinal epithelial cells as a result of radiation in the management of pelvic malignancies that may occasionally cause intestinal strictures. We present the case of a 60 year-old woman who had been diagnosed ten years before with endometrial adenocarcinoma, and who underwent hysterectomy with double adnexectomy and subsequent radiation therapy. The patient consulted for abdominal pain and ferropenic anemia of several years standing, and had negative results following radiographic and endoscopic conventional techniques, reason why she was subjected to a capsule endoscopy study that revealed the presence of an ulcerated ileal stricture, which caused the asymptomatic retention of the capsule within the ileum. A laparotomy was subsequently performed--the strictured segment was resected and the capsule retrieved. The histologic examination of the resected segment confirmed the capsule endoscopy-raised suspicion of radiation enteritis. This case shows the role capsule endoscopy may play in the diagnosis of this condition.

Abdominal Pain↗

Diagnostic yield and safety of capsule endoscopy.

INTRODUCTION: the capsule endoscopy (CE), from his approval, has become a first line diagnostic procedure for the study of the small bowel disease. The aim of this study is to report our experience since the implantation of this technique in our hospital. MATERIAL AND METHODS: retrospective review of the CE undertaken in Department of Endoscopy. There was gathered in every case the age, sex, motive of consultation, previous diagnostic procedures, capsule endoscopy findings and complication of the technique. One took to end a descriptive and analytical analysis. RESULTS: there was achieved a total of 416 explorations in 388 patients. The obscure gastrointestinal bleeding was the most frequent indication (83.30%) followed by suspected Crohn s disease (7.5%). Angiodisplasia was the endoscopic lesion more frequently detected (42.2%), especially, in patients with digestive bleeding of obscure origin (OR 3.13 p < 0.001), followed by the flebectasia (10.6%) and the ulcer suspicious of Crohn s disease (9.9%). The global diagnostic yield as for the detection of injuries was 77.34% with a case of "not defecation of the capsule" and therefore need of laparotomy. CONCLUSIONS: the capsule endoscopy is a technique consolidated and as his potential is known, his indications are extended. The obscure gastrointestinal bleeding is the most frequent indication and the angiodisplasia the most identified injury. Once known his diagnostic yield, larger studies are needed that assess the influence of capsule endoscopy on clinical outcoumes.

Capsule Endoscopy↗

Bioavailability of two metamizole (dipyrone) solutions as single doses of 2 g versus metamizole capsules.

OBJECTIVE: The aim of this study was to investigate the extent and the rate of absorption of metamizole, appearing in blood as methylaminoantipyrine (MAA), from a new oral solution and a parenteral solution administered by the oral route relative to capsules. METHODS: An open, randomized, 3 single-dose (2 g metamizole), crossover study with intervals of 7 days between periods was performed in 19 male and female healthy volunteers (age 22 - 45 years, body weight 49 - 88 kg, body height 156 - 189 cm). Metamizole metabolites were measured with an HPLC technique. The test formulations were considered bioequivalent with the reference formulation if the 90% confidence limits of the AUC0-->infinity and Cmax ratios and the tmax differences were within the range of 80 - 125%. RESULTS: The 90% confidence limits of the comparisons between capsules (reference) and oral solution, capsules (reference) and ampoules, and ampoules (reference) and oral solution were 98.5 - 117.8, 99.5 - 132.6 and 81.3 - 105.8 for AUC0-->infinity 98.7 - 119, 101.7 to 129.2, and 82.1 - 104.8 for Cmax, and 84.4 to 115.6, 100 - 105.6 and 70.3 - 100 for tmax, respectively. CONCLUSION: The oral solution was bioequivalent to capsules with regard both to the extent and the rate of MAA absorption. Metamizole as oral solution was bioequivalent to reference ampoules in the extent of MAA absorption, but absorption rate was faster. Ampoules showed a higher MAA bioavailability than capsules.

Administration, Oral↗

Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product.

OBJECTIVE: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been used successfully for more than a decade to treat human immunodeficiency virus (HIV) infection. The objective of the current study was to determine the bioequivalence between a generic capsule formulation of efavirenz and the innovator product. MATERIAL AND METHODS: A total of 41 healthy subjects (34 males and 8 females) received a single 200 mg oral dose of efavirenz as the generic (Ranbaxy-Efavirenz, Ranbaxy Laboratories Ltd.) and innovator (Sustiva, Bristol-Myers Squibb) capsule formulations under fasting conditions in a randomized, 2-way crossover study. Multiple blood samples were collected over 72 hours and plasma concentrations of efavirenz were assayed using an LC/MS/MS method. Pharmacokinetic (PK) parameters were calculated using non-compartmental methods. RESULTS: Plasma concentrations of efavirenz peaked within 2.5 hours and then declined in a multi-exponential manner for both formulations. At 72 hours post dose, all plasma concentrations of efavirenz were above the LOQ of the assay (10 ng/ml). Mean area under the curve from 0 - 72 hours (AUC0-72) and maximum plasma concentrations (Cmax) of efavirenz for the generic capsule formulation were 22,840 ng x h/ml and 1,199 ng/ml, respectively. Ratios and 90% confidence intervals of PK parameters between the two formulations were within 80.0 - 125.0%, suggesting that the two capsule formulations resulted in similar rate and extent of bioavailability under fasting conditions. Adverse events were similar in nature and frequency for the two formulations. CONCLUSIONS: Based on the above results, the generic capsule formulation of efavirenz developed by Ranbaxy should be as effective as the innovator product.

Administration, Oral↗

Initial experience with capsule endoscopy at a major referral hospital.

OBJECTIVES: To determine the utility of capsule endoscopy in patients referred for investigation of suspected disease of the small intestine. DESIGN AND SETTING: Single centre, prospective, cohort study from 4 July 2001 to 8 September 2002. PATIENTS: Sixty consecutive patients who underwent capsule endoscopy for investigation of suspected disease of the small intestine. MAIN OUTCOME MEASURES: Abnormal findings at capsule endoscopy. RESULTS: Examination of the entire small bowel was achieved in 46/60 patients (77%). Thirty-two of 47 patients (68%) referred with obscure gastrointestinal bleeding had positive findings. Seven of nine patients (78%) referred for investigation of suspected Crohn's disease had small bowel erosions or ulcers consistent with Crohn's disease. The capsule was not passed in one patient. CONCLUSION: Capsule endoscopy is a novel, minimally invasive and useful tool for the investigation of the small intestine.

Capsules↗

Adhesive capsulitis of the shoulder joint: usefulness of dynamic sonography.

We studied the value of dynamic sonography in adhesive capsulitis of the shoulder joint in patients with clinically suspected frozen shoulder. The sonographic criterion of adhesive capsulitis was continuous limitation of the sliding movement of the supraspinatus tendon against the acromion of the scapula. Arthrography was regarded as a gold standard in the diagnosis of adhesive capsulitis against which the sonographic results were compared. Among 23 patients with arthrographically documented adhesive capsulitis, sonographic examination showed limitation of movement of the supraspinatus tendon in 21. This sonographic sign therefore has a sensitivity of 91%, a specificity of 100%, and an accuracy of 92% for detecting adhesive capsulitis, making dynamic sonography a reliable technique for the diagnosis of this condition.

Adult↗

[Posterior continuous curvilinear capsulorhexis in congenital cataract with opaque posterior capsule].

OBJECTIVE: To study the management of the opacified posterior lens capsule in congenital cataract extraction with intraocular lens (IOL) implantation. METHODS: Posterior continuous curvilinear capsulorhexis was performed on 36 eyes of congenital cataract with opaque posterior capsule. After the removal of cortical material and implantation of IOL, a perforation was made near the center of the posterior capsule through the equator of IOL, Healon was directed toward the opening and injected into the interspace between the posterior capsule and the anterior limiting membrane of the vitreous, and a 4 mm diameter posterior capsulorhexis was performed with a forceps. RESULTS: All the eyes achieved a clear visual axis. There was vitreous prolapse in two eyes. IOL decentration did not occur in any case. CONCLUSION: Posterior continuous capsulorhexis could remain the integrity of the peripheral capsular bag with a clear visual axis in the eye with congenital cataract and an opaque posterior capsule.

Adolescent↗

Huperzine-A in capsules and tablets for treating patients with Alzheimer disease.

AIM: To compare the efficacy and safety between huperzine-A (Hup) in capsules and tablets for treating patients with Alzheimer disease (AD). METHODS: Using multicenter, prospective, double-blind, double-mimic, parallel, positive controlled and randomized methods, 60 patients meeting with the NINCDS-ARDRA criteria of AD were divided into 2 equal groups. Patients in the capsule group received 4 capsules of Hup (each contains 50 micrograms) and 4 tablets of placebo (lactose and starch inside); while the tablet group received 4 tablets of Hup (each contains 50 micrograms) and 4 capsules of placebo, p.o., twice a day for 60 d. All the patients were evaluated with a lot of related ranting scales, and physiological and laboratory examination. RESULTS: There were significant differences (P < 0.01) on all the psychological evaluations between 'before' and 'after' the 60-d trial of 2 groups, but there was no significant difference between 2 groups by group t test (P > 0.05). The changes of oxygen free radicals in 2 groups showed marked improvement. No severe side effect besides moderate to mild nausea was found in both groups. CONCLUSION: There is equal efficacy and safety between Hup in capsule and tablet for treating patients with AD, and Hup can reduce the pathological changes of the oxygen free radicals in the plasma and erythrocytes of patients with AD.

Aged↗

Diffusion anisotropy of the internal capsule and the corona radiata in association with stroke and tumors as measured by diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Diffusion-weighted MR images have enabled measurement of directionality of diffusion (anisotropy) in white matter. To investigate differences in the anisotropy for various types of pathologic findings and the association between the anisotropy of tracts and neurologic dysfunction, we compared the anisotropy of the posterior limb of the internal capsule and the corona radiata between patients with stroke and those with tumors and between patients with and without hemiparesis. METHODS: Thirty-three patients consisting of 11 with tumors and 22 with ischemic disease (16 acute infarction, four old infarction, and two transient ischemic attack) and nine control patients were studied with a 1.5-T MR imager. Diffusion-weighted images were obtained with diffusion gradients applied in three orthogonal directions. The diffusion anisotropy measurements were obtained from regions of interests defined within the internal capsule and the corona radiata. RESULTS: The diffusion anisotropy was significantly reduced in all internal capsules and coronae radiata involved by infarcts, tumors, and peritumoral edema compared with that of the control patients (P <.0001). This reduction was most prominent in the tracts involved by tumors (P <.05). The anisotropy of the internal capsules and coronae radiata was significantly decreased in cases with moderate-to-severe hemiparesis as compared with those with no or mild hemiparesis (P <.0001). Diffusion anisotropy tended to be also reduced in normal-appearing internal capsules and coronae radiata that were remote from the involved segment of the corticospinal tract. CONCLUSION: The degree of impaired diffusion anisotropy may vary in different pathologic conditions and correlate with neurologic dysfunction. The measurement of diffusion anisotropy may provide additional information relating to neurologic function and transneuronal effects.

Adolescent↗